3,4‐Dimethoxychalcone induces autophagy through activation of the transcription factors TFE3 and TFEB

EMBO Molecular Medicine

Jihoon Nah¹  Junichi Sadoshima¹  Wei Xie²  Federico Pietrocola²  Peng Liu²  Allan Sauvat²  Oliver Kepp²  Guo Chen²  Sylvie Lachkar²  Valentina Sica²  Guido Kroemer²  Maria Markaki³  Nektarios Tavernarakis³  Jelena Tadic⁴  Frank Madeo⁴  Tobias Pendl⁴  Lana Domuz⁴  Andreas Zimmermann⁴  Didac Carmona‐Gutierrez⁴  Martina Bergmann⁴  Sebastian J Hofer⁴ 

[1] Department of Cell Biology and Molecular Medicine Rutgers‐New Jersey Medical School Newark NJ USA;Gustave Roussy Cancer Campus Villejuif France;Institute of Molecular Biology and Biotechnology Foundation for Research and Technology‐Hellas Heraklion Greece;LInstitute of Molecular Biosciences University of Graz Graz Austria;

关键词: caloric restriction;    caloric restriction mimetic;    cardioprotection;    TFE3;    TFEB;   

DOI  :  10.15252/emmm.201910469

来源: DOAJ

【 摘 要 】

Abstract Caloric restriction mimetics (CRMs) are natural or synthetic compounds that mimic the health‐promoting and longevity‐extending effects of caloric restriction. CRMs provoke the deacetylation of cellular proteins coupled to an increase in autophagic flux in the absence of toxicity. Here, we report the identification of a novel candidate CRM, namely 3,4‐dimethoxychalcone (3,4‐DC), among a library of polyphenols. When added to several different human cell lines, 3,4‐DC induced the deacetylation of cytoplasmic proteins and stimulated autophagic flux. At difference with other well‐characterized CRMs, 3,4‐DC, however, required transcription factor EB (TFEB)‐ and E3 (TFE3)‐dependent gene transcription and mRNA translation to trigger autophagy. 3,4‐DC stimulated the translocation of TFEB and TFE3 into nuclei both in vitro and in vivo, in hepatocytes and cardiomyocytes. 3,4‐DC induced autophagy in vitro and in mouse organs, mediated autophagy‐dependent cardioprotective effects, and improved the efficacy of anticancer chemotherapy in vivo. Altogether, our results suggest that 3,4‐DC is a novel CRM with a previously unrecognized mode of action.

【 授权许可】

Unknown